Long-term objectives: Primate retinas have a yellow macular pigment that is thought both to enhance visual resolution and to protect the retina and retinal pigment epithelium (RPE) from oxidative damage. It is likely that some people with low pigment densities are at risk for chronic retinal damage and age-related macular degeneration. Our goal is to identify nutritional and retinal factors contributing to the protection of the retina by retinal carotenoids and Vitamin E. The idea that macular pigment contributes to refined visual resolution (acuity) in the fovea will be critically tested. Specific Aims: I. Identify factors underlying individual differences in density of macular pigmentation. Manipulate dietary levels of carotenoids while monitoring the resultant changes in the blood and the retinas of monkeys. Determine whether differences in macular pigment density are linked to differences in cone density in macaques and humans. II. Compare the spatial distributions of macular pigment carotenoids and Vitamin E. Compare the spatial distributions of the carotenoids comprising the macular pigment with the spatial distribution of Vitamin E in monkey and human retinas by microdissection and biochemical analyses. Determine whether Vitamin E is selectively associated with rod photoreceptors, which are known to be lost with aging. III. Measure the optical density profile of human macular pigment and assess its importance for visual performance. The spatial profile of human macular pigment density will be measured and compared with the spatial dimensions of the foveal depression. Noninvasive techniques will be utilized to study human macular pigment in vivo accurately and efficiently. Postmortem donor retinas will be studied in histological preparations to confirm the general features of the in vivo data. Individual differences in macular pigment density will be correlated with blood levels of macular pigment carotenoids. Subjects will include both genders and a cross section of ages and ethnic backgrounds from the local population. Visual resolution (acuity and contrast sensitivity) of subjects with high and low macular pigment will be tested to determine whether macular pigment improves visual performance. Methodology: The macular pigment carotenoids and Vitamin E will be measured in blood and retina by HPLC. In vivo measures of macular pigment in monkeys and some humans will be made by two-wavelength (photographic) reflectometry. The reflectometry data will be validated for monkeys by densitometry of retinal whole mounts, and for humans by psychophysical threshold testing. In older human subjects, much of the in vivo data will be gathered by psychophysical measurements. Retinal rod and cone distributions will be mapped by Nomarski imaging of retinal whole mounts. Health Relatedness: Older people are protected against the neovascular form of age-related macular degeneration by higher blood levels of carotenoids and other antioxidants. Thus manipulation or supplementation of the diet offers hope for preventive therapy. Our basic research project will provide essential data and techniques for deriving the maximum benefit from large, expensive clinical trials that are currently being initiated.